t(4;11)(q21;q23)

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t(4;11)(q21;q23)

Identity



	t(4;11)(q21;q23) ) G-banding (left) - Courtesy Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap, http://www.slh.wisc.edu/cytogenetics>; R- banding (right) - Jean Loup Huret (top), - Courtesy Christiane Charrin (middle), - Courtesy Hossein Mossafa (bottom and FISH).

Clinics and Pathology

Disease	ALL mainly
Phenotype / cell stem origin	B-ALL (L1 or L2), biphenotypic AL, at times ANLL (M4/M5 types maily); has been found in treatment related leukaemia; T-ALL as an exception
Epidemiology	children (including infants: named a congenital leukaemia when before 1 yr or 2 yrs of age) and adults; half cases are under 4 yrs, 1/3 under 1yr; unbalanced sex ratio in cases < 4 yrs (1M/2F); 2 to 5% of ALL
Clinics	organomegaly, CNS involvement not rare; can be secondary to epipodophyllotoxins (antitopoisomerase drugs for various cancers treatment); high WBC (median around 200 X 10⁹/l), anaemia, thrombocytopenia; 90% blasts in blood
Cytology	typically CD19+; may be accompanied with myeloid markers
Treatment	bone marrow transplantation is highly indicated, as the prognosis is very poor
Prognosis	CR is obtained but is promptly followed by relape; median survival: 7 mths in adult cases, 9 mths in children

Cytogenetics



	i(7q) R- banding - Jean-Loup Huret (left), - Courtesy Christiane Charrin (right).

Additional anomalies	in 1/4 of cases at diagnosis, clonal evolution to hyperploidy: i(7q) in 10%, +X, + Mar, +6, +8, +19, +21, +13, +10, +14; no difference in outcome
Variants	three way complex t(4;11;Var) exist and showed that the crucial event lies on der(11)

Genes involved and Proteins

Gene Name	AF4
Location	4q21
Dna / Rna	10.5-12 kb mRNA
Protein	contains a nuclear targeting sequence; nuclear localisation; function: transcription activator

Gene Name	MLL
Location	11q23
Dna / Rna	21 exons, spanning over 100 kb; 13-15 kb mRNA
Protein	431 kDa; contains two DNA binding motifs (a AT hook, and Zinc fingers), a DNA methyl transferase motif, a bromodomain; transcriptional regulatory factor; nuclear localisation

Result of the chromosomal anomaly

Hybrid gene

Description	5' MLL-3' AF4; variable breakpoints
Transcript	12kb

Fusion Protein

Description	e.g. 2319 amino acids; 240 kDa; N-term AT hook and DNA methyltransferase from MLL fused to AF4 C-term; the reciprocal ( AF4-MLL) may or may not be expressed; quite similar to the MLL/ENL fusion protein found with t(11;19)
Expression Localisation	nuclear localisation

External links

Other database	t(4;11)(q21;q23)	Mitelman database (CGAP - NCBI)

To be noted

you may also have a glance at 11q23 rearrangements, which gives an overview of related diseases.

Bibliography

Cytogenetic features of infants less than 12 months of age at diagnosis of acute lymphoblastic leukemia: impact of the 11q23 breakpoint on outcome: a report of the Childrens Cancer Group.

Heerema NA, Arthur DC, Sather H, Albo V, Feusner J, Lange BJ, Steinherz PG, Zeltzer P, Hammond D, Reaman GH

Blood. 1994 ; 83 (8) : 2274-2284.

Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases.

Pui CH, Frankel LS, Carroll AJ, Raimondi SC, Shuster JJ, Head DR, Crist WM, Land VJ, Pullen DJ, Steuber CP

Blood. 1991 ; 77 (3) : 440-447.

Twenty-three cases of acute lymphoblastic leukemia with translocation t(4;11)(q21;q23): the implication of additional chromosomal aberrations.

Schoch C, Rieder H, Freund M, Hoelzer D, Riehm H, Fonatsch C

Annals of hematology. 1995 ; 70 (4) : 195-201.

Acute leukemia with chromosome translocation (4;11): 7 new patients and analysis of 71 cases.

Lampert F, Harbott J, Ludwig WD, Bartram CR, Ritter J, Gerein V, Neidhardt M, Mertens R, Graf N, Riehm H

Blut. 1987 ; 54 (6) : 325-335.

Acute leukemia with chromosome translocation (4;11): 7 new patients and analysis of 71 cases.

Lampert F, Harbott J, Ludwig WD, Bartram CR, Ritter J, Gerein V, Neidhardt M, Mertens R, Graf N, Riehm H

Blut. 1987 ; 54 (6) : 325-335.

Contributor(s)

Written	12-1997	Jean-Loup Huret

This paper should be referenced as such :

Huret JL . t(4;11)(q21;q23). Atlas Genet Cytogenet Oncol Haematol. December 1997 .
URL : http://AtlasGeneticsOncology.org/Anomalies/t0411.html

This paper is referenced by INIST as such :

http://documents.irevues.inist.fr/bitstream/handle/2042/32069/12-1997-t0411.pdf [ Bibliographic record ]

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indexed on : Sat Mar 9 12:37:11 CET 2013

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